The Effects on Human Health of Subtherapeutic Use of Antimicrobials in Animal Feeds (1980) / Chapter Skim
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Appendix G: Transmission of Food-Borne Diseases-Implications of the Subtherapeutic Use of Antimicrobials
Appendix G: Transmission of Food-Borne Diseases-Implications of the Subtherapeutic Use of Antimicrobials
Pages 203-261
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From page 203... ...
botulinum food poisoning, because it is a much more serious disease in terms of its life-threatening potential, are much more accurate. However, since there is no known or suspected connection between _ botulinum food poisoning and the use of antibiotics at subtherapeutic levels in animal feeds, it will not be discussed further in this paper.
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From page 204... ...
food-borne disease outbreaks in the United States.
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7% of the isolates from nonhuman sources. It is by far the most frequently isolated serotype.
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TOTAL 66 267 5921,063 4343,261 PERCENT OF TOTAL OF ALL SEROTYPE S ISOLATED 39 44 6881 6162 TOTAL OF ALL SEROTYPES ISOLATED 168 608 8661,313 7135,243 oFrom CDC, 1979. Also includes isolates from other animals and environmental samples.
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From page 207... ...
207 TABLE 3 10 Sa~oneZZa Serotypes Most Frequently Isolated from Human Sources, 1977 1 i SerotypeNumber Percent Rank in 1976 typhimurium9,690 35.3 1 newport2,187 8.0 4 Heidelberg1,741 6.3 2 enteritidis1,472 5.4 5 infantis1,304 4.7 6 agona1,229 4.5 3 saint-paul580 2.1 7 typhi549 2.0 8 montevideo470 1.7 12 oranienburg440 1.6 9 TOTAL19,662 71.6 TOTAL OF ALL SEROTYPES27,462 a From CDC, 1979. bIncludes var.
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From page 208... ...
By plating the fecal samples on agar containing nalidixic acid and chlortetracycline, it was possible to learn whether the infecting salmonellae had acquired tetracycline resistance from the tetracycline-resistant E cold which the pigs were known to have.
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From page 209... ...
FIGl~RF 1. Summary of Salmonella typhimurium isolations from swine.
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From page 210... ...
210 J m 7r Unmedicated 6 4 \~ 1 lo Oxytetracycline _ 150 g/ton \ \ Neomycin + Oxytetracycline, ~50 9 each/ton I I I 7 10 14 21 28 1 1 , DAYS (Postinoculation with 1.4 X 1 o1 1 salmonellae)
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From page 211... ...
The third group was not medicated. After 5 days of medication, each calf 9as infected orally via stomach tube with approximately 6.5 x 10 cfu of a nalidixic-acid-resistant, antibiotic-sensitive strain of Salmonella typhimurium of bovine ori gin.
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FIGURE 3. Salmonella typhimurium isolated from feces of infected .
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213 6 . ~ 2 ~ 2 LL J m 4 o /\lonmedicated Oxytetracycl ins, 350 mg/head/day r~~l ~~ I -- -r~~~'~l~~ 2 4 7 10 14 21 28 Neomycin + \ Oxytetracycline, 350 mg each/head/day ~' \/ ~-~ DAYS (Postinoculation with 1.10 X 1 o1 ]
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From page 214... ...
On the sixth day after medication had begun, each chick in one of the medicated and one of the unmedicated groups was infected orally with approximately 6.8 x 109 cfu of a nalidixic acid-resistant, antibiotic-sensitive strain of Salmonella tYPhimurium of chicken origin. Droppings from each bird in the infected groups were analyzed for Salmonella content at intervals for 57 days.
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FIGURE 5. Salmonella typhimurium i so let ions from droppings of chickens inoculated wi th 6.
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These experiments provide evidence that the use of subtherapeutic levels of tetracycline in the feed of swine, calves, and chickens do not increase the number of animals shedding Salmonella or the total number of salmonellae shed nor does it prolong the duration of shedding or select for resistant strains when the infecting organism is sensitive to antibiotics. Williams et al.
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From page 217... ...
. Final Weight' kg Feed: Gain Nonmedicated 1.95 2.
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From page 218... ...
6 ^ .` c = 0 4 ~ 3 m o 218 \ \ Nonmedicoted Iowan + 1 °~7~ g earn Oxvtetracyci lne, ~0 Ion 2 4 7 10 14 21 28 DAYS (Postlnoculallon with 2.g X 1011 salmonellae)
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From page 219... ...
219 1 00 80 Cal O 60 LO > 40 oh o Cal 1~ 20 C' LU Cal o \ Nonmedicated Ch lortetracycl ine, 200 g/ton -R 4 5 _ ~ 6 7 8 AGE OF BIRDS IN WEEKS FIGURE 7. Percent of contact birds positive for Salmonella typhimurium by di rect plating or af ter enrichment.
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From page 220... ...
However, when the pigs were infected with an antibiotic-resistant strain and were then given feed containing chlortetracycline, they shed a greater quantity of salmonellae for a longer time than did the pigs on unmedicated feed. Salmonellae spread to uninfected pigs that were exposed to pigs with antibiotic-resistant salmonellae.
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From page 221... ...
221 TABLE Mortality of Chicks Infected with Strains of SaZmoneZZa typh~muri~m that were Sensitive or Resistant to Chlortetracycline When Receiving _ed Treated with Chlortetracycline or Unmedicated Feeda Type of Feed Mortality, by sensitivity of ~aZmoneZZa Sensitive Resistant b nonmedicated 90/185 92/217 (48.6%)
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222 TABLE 6 10 SahmoneZZa Serotypes Most Frequently Isolated from Food Animals, 1975 through 1977 a 1975 No. of Isolates Serotype senftenberg 1976 120 1977 Serotype No.
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Heidelberg is one of the most frequently isolated serotypes: phage typing of isolates from animals and from cases of salmonellosis in humans would be necessary to prove that the infections were caused by salmonellae of animal origin.
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224 TABLE 7 10 Sa1~none1~1'a Serotypes Most Frequently Isolated from Dietary Items for Human Consumption, 1975 through 1977 ~ 1975 1976 1977 No.
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of No. of Isolates Serotype Isolates Serotype Isolates typhimurium6,888 typhimurium7,347 typhimurium9,690 newport1,550 heidelberg1,962 newport2,187 enteritidis1,519 agona1,461 heidelberg1,741 heidelberg1,474 newport1,336 enteritidis1,472 agona1,333 enteritidis1,219 infantis1,304 infantis1,194 infantis1,014 agona1,229 saint-paul833 saint-paul545 saint-paul580 typhi551 typhi529 typhi549 oranienburg446 oranienburg465 montevideo470 javiana426 muenchen374 oranienburg440 TOTAL16,264 16,752 19,662 PERCENTAGE OF TOTAL SERO TYPES ISOLATED69 72 72 TOTAL SEROTYPES ISOLATED23,445 23,285 27,462 CDC, 1976b, 1977d, 1979.
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S typhimurium was infrequently isolated from cattle feed.
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From page 227... ...
Heidelberg, thompson, newport, and saint-paul were isolated in each of the 3 years. These serotypes, except for thompson, were among the seven most frequently isolated from humans in each of the 3 years.
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From page 228... ...
of No. of Serotype Isolates Serotype Isolates Serotype Isolates saint-paul 6 typhimurium 15 typhimurium 8 typhimurium 2 typhi 5 infantis 4 enteritidis 2 heidelberg 5 agona 3 typhi 2 enteritidis 3 heidelberg 2 thompson 2 saint-paul 2 san-diego 2 oranienburg 1 bovis-morbificans 2 typhi 2 tennessee 1 newport 2 bredeney 2 reading 1 typhimurium var.
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From page 229... ...
Large amounts of ground beef, cold cuts, and frankfurters are consumed in the United States. Because the manufacture and sale of these products require more handling than do cuts of beef or pork, it is desirable to analyze CDC's food-borne disease surveillance data on these foods (CDC, 1975~.
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Table 11 lists the 10 most frequently isolated serotypes from humans in England and Wales and in the United States. Six of the 10 most frequently isolated serotypes are the same in both lists as are three of the first four ranked.
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231 TABLE 10 Surveys of Salmonellae in Raw Beef Patties, Luncheon Meat, and Frankfurters, 1972 through 1975 a Product Sampl es Examined Sample s Positive Raw beef pa t ties Raw tr immings 6 90 1 Raw finished patties 735 3 Frankfurters Raw trimmings 842 56 Cooked finished frank- 690 0 furlers Sliced luncheon meat Raw trimmings 936 69 Cooked, sliced luncheon 456 0 meat Lax From CDC, 1975
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of Isolates Serotype United States 1977 , ~ pro tvr)
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From page 233... ...
However, when it does reach the consumer, mishandling of meat and meat products can result in multiplication of the organisms to the point that the consumer becomes infected and an outbreak occurs. But examination of the information on which these conclusions are based produces no evidence that the use of subtherapeutic levels of tetracyclines or penicillin in animal feed played any role in the size of the reservoir, the spread of the salmonellae, or in any of the steps in transmission to the consumer.
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From page 234... ...
They said, An urban reservoir of resistance transfer factor could exist equally as well as the postulated animal reservoir. It is difficult to reconcile the knowledge that the highest incidence of salmonellosis occurs in young children and infants in slum areas in New York City and the finding that the highest frequency of resistant Salmonella strains occurs in municipal hospitals serving these areas, with the hypothesis that Salmonella in general and resistant strains (or the resistance transfer factor)
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From page 235... ...
(27) Antibiotic human animal human animal human animal human animal .
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From page 236... ...
236 TABLE 13 Effect of Oxytetracycline (OTC) Water Medication on the Rate of Development of Escheriahia coZi Resistance In Vivo to Tetracyclines, Dihydrostreptomycin, Sulfamethazine, and Ampicillina No OTC OTC, 50 ppm OTC, 500 ppm Percentage Resistant Percentage Resistant Percentage Resistant Day Tc~ Dhs~ Size Ampe Tc Dhs Smz ~Tc Dhs Smz Amp -6 0 0 0 0 0 0 0 0 0 0 0 0 -2 3 6 6 6 0 0 0 0 0 0 0 0 o f - O O O O O O O O +1 0 0 3 0 55 50 55 23 66 66 0 +2 0 0 0 0 94 94 94 16 100 100 0 0 +3 19 19 16 9 100 100 100 3 100 100 0 0 +4 3 0 0 0 97 97 97 19 100 100 3 0 +5 0 0 0 0 100 100 100 13 100 100 0 0 +6 0 0 0 0 94 94 94 3 100 100 0 0 From Luther et al., 1974, with permission from the authors and Miles Labora tories, Ltd.
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From page 237... ...
The development of resistance to ampicillin in S typhimurium in calves and in humans would seem to be separate phenomena, and neither the use of antibiotics in feed nor therapeutic use in calves has influenced resistance in strains of S typhimurium from humans in the northeastern United States.
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From page 238... ...
238 TABLE 14 Antibiotic-Resistant Strains of Sahnon~ZZa tuphinn~ Isolated from Calves" No. of Pergentage resistant Percentage with Year Isolates Amps colic Kma Nm e smf Tog transterAble R factors 1973 37 16 3 95 95 100 100 38 1974 40 33 3 87 83 97 95 49 1975 35 43 5 80 69 78 86 60 1976 23 74 9 96 87 100 100 87 a b d e From Timoney, 1978, with permission from the author and the University of Ch icago Pres s.
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239 TABLE 1 5 Antibiotic-Resistant SabnaneZZa typhi77rur:? ~n Percentage of Resistant Isolates, by Study (Total of Isolates Tested ~ 1.
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ium IN ENGLAND An epidemic of antibiotic-resistant Salmonella typhimurium phage type 29 occurred in calves in England starting in 1964, peaking in 1965, and subsiding in 1966. This infection spread to humans.
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241 TABLE 16 SaZmone[Za agona Isolated from Human and Nonhuman Sources, 1969-1977 Number of Isolates Year of Study Human Nonhuman 19690 3 19704 5 197144 34 1972524 NAb 1973864 NA 19741,037 NA 19751,333 45 19761,461 40 1977 From CDC, 1976b, 1977d, 1979. b NA = Data not available 1,229 271 .
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From page 242... ...
Finally, there seems to be no evidence that the use of tetracyclines and penicillin in animal feed play any adverse role in the development of salmonellosis in animals or humans or in food-borne outbreaks of salmonellosis in humans. ANTIBIOTIC-RESISTANT Esoherzahia oofi IN HUMANS AND DOMESTIC ANIMALS In the Statement of Policy and Interpretation Regarding Animal Drugs and Medicated Feeds (FDA, 1973)
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The birds in one of these cages were given feed containing oxytetracycline; the other plain feed.
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At the University of Bristol in England, a second group investigated the possible colonization of human intestines by E cold of animal origin.
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These experiments suggest that the colonization of the human intestine by E cold of animal origin is a rare event.
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From page 246... ...
Walton addressed this question in another study (Walton and Lewis, 1971) in which 25 samples from fresh minced beef and sausage and 25 from cooked boiled ham and roast pork obtained from 25 butcher shops were examined for contamination with antibiotic-resistant fecal colifonm organisms.
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used established donors of enterotoxin-plasmids to attempt the simultaneous transfer of Ent plasmids and R factors. The transfer plasmids was not de tected when antibiotic-resistant transconjugants were selected.
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From page 249... ...
cold carrying an Ent plasmid will survive longer and in greater _ ~ numbers than would those of a homogenic strain without the Ent plasmid. The presence of a K99 plasmid, which confers the ability to colonize the intestinal tract of young calves, did not greatly increase the ability of the E
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From page 250... ...
There seems to be no connection between these diseases and the use of antibiotics in animal feed. STAPHYLOCOCCAL FOOD POISONING _ Staphylococcal enterotoxin is one of the two most frequently reported causes of outbreaks of food-borne disease.
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o ~1 on Id on · i on o :^ ID Q a, 0 U: Cal o ¢ to to 0 o o o ED CQ _' U)
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From page 252... ...
Domestic animals and pets can become carriers of strains of staphylococci of phage types that are frequently associated with human disease (Pagano et al., 1960~. During the school year 19561957 an unusual number of senior students at the University of Pennsylvania School of Veterinary Medicine were afflicted with furuncles, deep cutaneous abscesses, cellulitis, and paronychia.
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From page 253... ...
A determination of the biological and phagetypes of the methicillin-resistant strains suggested that they were actually strains from humans and might have had a common human source, but that seems highly speculative. In summary, food poisoning due to Staphylococcus aureus enterotoxin is frequently reported in the United States, England, and Wales.
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From page 254... ...
It often involves meat products, but upon investigation, it is frequently found that the food was contaminated by a human carrier or one with a Staphylococcus-infected lesion. Staphylococci of phase types usually considered to be of human origin have been found in pets and dairy cows.
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From page 255... ...
1968a. Drug resistance in Salmonella typhimurium and its implications.
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From page 256... ...
1971. Antibiotic sensitivity of Escherichia cold isolated from animals, food, hospital patients, and normal people.
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From page 257... ...
1960. The emergence of resistant strains of Salmonella typhimurium in the tissues and alimentary tracts of chickens following the feeding of an antibiotic.
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1976. Influence of antibiotic-suppl~mented feed on occurrence and persistence of Salmonella typhimurium in experimentally infected swine.
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1971. Survey of infectious multiple drug resistance among Salmonella isolated from animals in the United States.
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1978. Epidemic spread of a chloramphenicol-resistant strain of Salmonella typhimurium phage type 204 in bovine animals in Britain.
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From page 261... ...
1978. Effect of feeding chlortetracycline on the reservoir of Salmonella typhimurium in experimentally infected swine.
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